This proposal intends to study the type II alveolar epithelial cells both in vivo and in vitro. For the first time, a method for isolating the viable type II cells has been developed in the principal investigator's laboratory. It is the purpose of this proposal to obtain normal basic structural and metabolic data on the isolated type II cells and to extend the scope of the study to some pathological conditions such as hypoxia, hyperoxia and hypercapnea both in vivo and in vitro. In the future we intend to utilize the information obtained from this proposal for the studies of many pathological conditions known to affect type II cells pathologically and biochemically. This proposal is composed of 4 projects. The first project deals with metabolic and structural study on the isolated type II cells in freshly recovered state. Specifically we intend to investigate pulmonary surfactant, mostly dipalmitoyl lecithin, synthesis and secretion by the type II cell in vitro. Metabolic studies include precursor-product relationship by using radioactive precursors, enzyme studies pertinent to dipalmitoyl lecithin synthesis, and qualitative and quantitative analysis of various lipid classes. The structural aspect will include freeze-etch and fracture study as well as regular transmission electron microscopy. Project II deals with the establishment of short-term culture medium that ensures metabolic and structural stability for up to 30 days by using the criteria developed in Project I. Project III is the study of the effect of hypoxia, hyperoxia and hypercapnea in vivo and in vitro in order to gain some insight into the mechanism on the derangement of the lipid synthesis and secretion in type II cells. The fourth project deals with the defense mechanism of the alveoli, utilizing the secretory product of type II cells. BIBLIOGRAPHIC REFERENCES: Kikkawa, Y., Yoneda, K., Smith, F., Packard, B. & Suzuki, K. The Type II Epithelial Cell of the Lung II. Chemical Composition and Phospholipid Synthesis. Lab. Invest. 32,295-301, 1975. Smith, F., Packard, B. & Kikkawa, Y. Lecithin Synthesis in Alveolar Type II Cells and Pulmonary Macrophages. Amer. Rev. Resp. Dis. 111,925,1975.